Embolization systems

ABSTRACT

Provided is a device for delivery into a body lumen having a longitudinally extending stem and a plurality of bristles extending generally radially outwardly from the stem. The device includes at least two different groups or types of bristles.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority from U.S. ProvisionalApplication No. 61/787,223, filed on Mar. 15, 2013, the entirety ofwhich is incorporated by reference herein.

FIELD OF THE DISCLOSURE

Embodiments of the present disclosure relate to devices and systems forembolization.

BACKGROUND

Migration of conventional embolization coils occurs 4-14% oftranscatheter embolizations [2,3]. Non-target embolization is an outcomeof coils migration, the impact of which depends on the final location ofthe coils. In the venous system, the consequences can be catastrophicwith literature indicating that coils can migrate into the renal vein,right atrium of the heart, lung (pulmonary artery). Percutaneousretrieval of the coils is technically very challenging and frequentlycannot be attempted as the coils are often entrapped within the organsand tissue.

Coil migration occurs for various reasons:

-   -   Technical error: release of a coil or coil pack too distal or        proximal to an adjoining larger vessel or plexus [6,7]    -   High blood flow areas can cause the coil to migrate.    -   Coil: vessel mismatch. The coils are undersized, hence will not        injure the vessel wall, will not induce thrombosis, and are        likely to migrate. Or the coils are oversized and will act like        a guide-wire and pass further distally into the vessel [8,9].    -   Vessel dilation: coil migration can occur due to a disparity in        the size of coils and dilated vessels, which can change in their        diameters depending on vessel hemodynamics [5].    -   Coils impart a very low radial (anchor) force on the lumen, once        a clot forms within the coil, blood flow can force it to        migrate.

The profile of the embolization device and delivery system is a criticalsuccess factor in successfully accessing target embolization locationse.g. the iliac arteries are frequently tortuous in the presence ofabdominal aortic aneurysms [8]. To combat this issue today,microcatheters are often employed in difficult or tortuous anatomy whereuse of standard catheters may induce spasm and lead to a failedembolization procedure [8]. Additionally different stages in a proceduremay require catheters with different mechanical properties e.g.accessing a visceral vessel, particularly in the presence of diseased ortortuous arteries, may require a catheter with a high degree ofstiffness and torque control. In general, the lower the profile of thedevice and delivery system, the greater the accessibility of the deviceinto tortuous and higher order vessels. A lower profile device reducesthe diameter of catheter required for delivery and lowers the risks ofaccess site infections, hematomas and lumen spasm.

Dependent on the clinical application of the device, variable anchorforces may be required to prevent migration of the prosthesis e.g.arterial and venous applications have variable blood flow rates andforces. This in turn, will lead to a compromise in terms of profilesince larger fibres, which better anchor the bristle device in thelumen, will require a larger catheter for delivery.

The technique generally used to embolise vessels today is to insert ametallic scaffold (coil, plug) into the target vessel, to cause athrombus that adheres to the scaffold, relying on the thrombus to induceblood cessation and eventually occlude the vessel. In general, availableembolization technology does not interfere with or interact with bloodflow densely enough across the vessel cross section to induce rapid,permanent vessel occlusion.

Using technology available today, the physician will often have toprolong a specific duration of time for the technology to induceocclusion. In one approach the physician inserts coils and then waits 20minutes for the coils to expand and cause vessel occlusion [1].

The restoration of the lumen of a blood vessel following thromboticocclusion by restoration of the channel or by the formation of newchannels, is termed recanalisation. Recanalisation can occur due to,coil migration, fragmentation of the embolisation material, andformation of a new vessel lumen that circumvents the occlusion [9].Recanalization rates vary by procedure and embolic agent, ranging from10% to portal vein embolization to 15% for pulmonary arteriovenousmalformations to 30% for splenic artery embolization [12,14,15]

SUMMARY

Various embodiments of the disclosure may include one or more of thefollowing aspects.

In accordance with one embodiment, there is provided a bristle devicefor delivery into a body lumen comprising a longitudinally extendingstem and a plurality of bristles extending generally radially outwardlyfrom the stem wherein there are at least two different groups or typesof bristles.

In one embodiment bristles of one group have a thickness which isdifferent than the thickness of bristles of another group.

In one case one group of bristles is of a different material than thematerial of another group of bristles.

One group of bristles may be more flexible than another group ofbristles.

In one embodiment one group of bristles are interspersed with anothergroup of bristles.

In one case one group of bristles are adapted for anchoring the bristledevice in a body lumen. An anchoring group of bristles may be providedat the proximal and/or distal end of the device.

In one embodiment one group of bristles are adapted for occlusion of alumen. The occlusion group of bristles may be located intermediate theproximal and distal ends of the bristle device.

In one case at least some of the occluding group of bristles areinterspersed with the anchoring group of bristles so that the number ofoccluding bristles increases from the distal end towards the proximalend of the device.

In one embodiment some of the anchoring groups of bristles areinterspersed with the occluding group of bristles so that the number ofanchoring bristles decreases from the distal end towards the proximalend of the device.

In one case one group of bristles extend radially outwardly to onediameter and another group of bristles extend radially outwardly toanother diameter which is different than the diameter of the first groupof bristles.

According to a further aspect, one group of bristles are aligneddifferently than another group of bristles.

At least some of the bristles may be adapted for delivery of atherapeutic agent. The agent delivery bristles may be at least partiallycoated with a therapeutic agent. Alternatively or additionally at leastsome of the bristles contain a therapeutic agent. In one case thebristles comprise striations and/or holes for containing a therapeuticagent.

In another aspect the disclosure provides a bristle device loadingsystem comprising:—

-   -   a bristle device for delivery into a body lumen;    -   a loading tube; and    -   a loading element for loading the bristle device into the        loading tube.

In one embodiment the loading element is detachably mountable to thebristle device.

In one case the loading element comprises a loading wire.

The system may comprise a delivery catheter for receiving the bristledevice from the loading tube. The loading element may be adapted forloading the bristle device from the loading tube into the deliverycatheter. The loading element may also be adapted for deploying thebristle device from the delivery catheter.

In one embodiment the system comprises a taper or a funnel to aidloading of the bristle device into the loading tube and/or the deliverycatheter.

In one case the taper or funnel comprises an extension of the loadingtube.

In one embodiment the loading tube comprises means for re-orientating atleast some of the bristles of the bristle device as the bristle deviceis passing through the loading tube.

The re-orientation means may comprise at least one hole in the wall ofthe loading tube through which the bristles may temporarily extendradially outwardly for transition from a first configuration in whichthe bristles are aligned at a first angle to the longitudinal axis ofthe loading tube and a second configuration in which the bristles arealigned at a second angle to the longitudinal axis of the loading tube.In one case, in the second configuration the bristles extend generallyin an opposite direction to the orientation of the bristles in the firstconfiguration.

The re-orientation means may comprise at least one slot in the wall ofthe loading tube.

In a further aspect the invention provides a method for loading abristle device into a delivery catheter comprising the steps of:—

-   -   providing a bristle device, a loading tube and a loading        element;    -   using the loading element, delivering the bristle device into        the loading tube; and    -   using the loading element, delivering the bristle device into a        delivery catheter.

The method may comprise deploying the bristle device from the deliverycatheter using the loading element.

In one case the loading element is releasably mountable to the bristledevice and the method comprises mounting the loading element to thebristle device for loading the bristle device into the loading tubeand/or for loading the bristle device into the delivery catheter and/orfor deploying the bristle device from the delivery catheter, and/or forretrieving a deployed bristle device.

In one case after delivery of the bristle device into the loading tubeand/or into the delivery catheter and/or after deployment of the bristledevice, the loading element is detached from the loading element.

In one embodiment the loading element is re-attached to the bristledevice for retrieval of the bristle device.

The disclosure also provides a bristle device which confirms to a vessellumen. The bristle device in this embodiment has a larger diameter thanthe target vessel but the bristles do not deliver sufficient force toperforate the vessel.

The disclosure further provides a bristle device which, when implantedimposes a greater resistance to flow in the axial direction compared tothe radial (lateral) direction.

In another aspect the invention provides the use of a bristle device tocause vascular occlusion for the treatment of haemorrhoids.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate certain exemplary embodiments ofthe present disclosure and, together with the description, serve toexplain the principles of the present disclosure. As such, those skilledin the art will appreciate that the conception upon which thisdisclosure is based may readily be used as a basis for designing otherstructures, methods, and systems for carrying out the several purposesof the present disclosure. It is important, therefore, to recognize thatthe claims should be regarded as including such equivalent constructionsinsofar as they do not depart from the spirit and scope of the presentdisclosure.

FIG. 1 is an illustration of a bristle device according to the inventionwith two types of bristles having different diameters;

FIG. 2 illustrates the device of FIG. 1 loaded into a tube;

FIGS. 3 and 4 illustrate bristles of different diameters;

FIGS. 5 to 8 illustrate bristle devices with bristles of differentdiameters;

FIG. 9 illustrates a bristle device with two types of bristles (dashed,continuous, interspersed and evenly distributed);

FIG. 10 illustrates the uniform anchoring force applied by the device ofFIG. 9;

FIG. 11 illustrates a bristle device in which two different types ofbristles are used;

FIG. 12 illustrates the variation in the anchoring force applied by thedevice of FIG. 11;

FIG. 13 illustrates another bristle device with a gradual variation inbristle density;

FIG. 14 is a diagram illustrating the variation in the force applied bythe device of FIG. 13;

FIGS. 15 and 16 are illustrations of another bristle device of theinvention in collapsed and unconstrained configurations;

FIGS. 17a to 17c illustrate the effect of time in the collapsedcondition on unconstrained geometry of a bristle device, when deployed;

FIGS. 18 to 24 illustrate a bristle device loading system according tothe invention in various configurations of use;

FIGS. 25 and 26 illustrate a tapered loading tube;

FIGS. 27 and 28 illustrate differing bristle orientations with respectto flow;

FIGS. 29 and 30 show a loading tube with a re-orientation featureaccording to the invention;

FIGS. 31 to 33 illustrate the loading tube of FIGS. 29, 30, in use;

FIG. 34 shows a bristle device with bristles pointing in opposeddirections;

FIG. 35 illustrates vessel perforation by portion of a bristle device;

FIG. 36 illustrates a bristle device with flexible fibres for vesselconformance;

FIGS. 37 to 39 illustrate alternative bristle devices with geometries toconform with particular vessel shapes;

FIG. 40 illustrates deformation of a vessel by a bristle device;

FIG. 41 illustrates a bristle device with length and diameterattributed;

FIG. 42 shows the negative effect of a low length to diameter ratio;

FIG. 43 illustrates a bristle device with a high length to diameterratio;

FIG. 44 illustrates a bristle device with distal anchoring fibres;

FIG. 45 shows the use of longer bristles at the ends acting asstabilisers;

FIG. 46 illustrates a bristle device with stabilisers on both ends;

FIGS. 47 to 49 illustrate a delivery system having a slot detachmentmechanism;

FIGS. 50 to 52 illustrate a bristle device with another detachmentfeature;

FIGS. 53, 54 and FIGS. 55, 56 illustrate bristle devices with furtherdetachment features;

FIGS. 57 and 58 illustrates a bristle device with non uniform bristlelengths.

FIGS. 59 and 60 illustrate another bristle device with a curved core anda diameter less than that of the target lumen;

FIGS. 61 and 62 show a further bristle device with a curved core and adiameter greater than that of the target lumen;

FIGS. 63 and 64 show a bristle device with a curved core and variablebristle lengths;

FIGS. 65 and 66 show a bristle device with bristles pointing inwardlyfrom a retaining wire;

FIG. 67 illustrates the effect of core diameter on flexibility;

FIG. 68 shows a bristle device with flexible sections and application tobifurcated vessels;

FIG. 69 illustrates the control of fluid using a bristle device;

FIGS. 70 to 72 illustrate the uses of bristle devices;

FIG. 73 are typical patterns of contact caused by coils;

FIGS. 74 and 75 illustrate the effect of oversizing on surface areadivided by a bristle device;

FIG. 76 illustrates the impact of bristle density on vessel damage;

FIG. 77 illustrates a denudation technique using a bristle device;

FIGS. 78 to 81 illustrate bristle devices for use in treatment of aseptal defect;

FIGS. 82 to 85 illustrate steps in deployment of the devices of FIGS. 78to 81;

FIGS. 86 and 87 illustrate a bristle device with length modifyingcomponents;

FIG. 88 illustrates deployment of the device of FIGS. 86, 87;

FIG. 89 shows a bristle device with a loosely wound core;

FIG. 90 shows techniques of pushing a delivery catheter to decreaseadjustable sections between bristle segments;

FIG. 91 illustrates bristle devices with a through flow path;

FIG. 92 depicts the flow path in a twisted bristle device;

FIG. 93 illustrates overlapping bristle sections to inhibit flow;

FIG. 94 shows another bristle device with fibres that increase involume;

FIG. 95 illustrates a bristle device with microfibers for improvedthromogenicity;

FIG. 96 shows an embolus detaching from a bristle device;

FIG. 97 illustrates a bristle device deployed to treat a cerebralaneurysm;

FIGS. 98 to 100 illustrate bristle devices with gaps to limit clotfragments;

FIGS. 101 to 104 show various bristle tips to prevent vessel perforationupon or after deployment;

FIG. 105 illustrates the assembly of a bristle device to a deliverywire;

FIG. 106 illustrates a bristle device deployed in a lumen;

FIGS. 107 to 109 show various retrieval systems for retrieving a bristledevice;

FIGS. 110 to 112 illustrates various degradable bristle devices;

FIG. 113 illustrates the manufacture of a twisted wire bristle device;

FIG. 114 shows a twisted wire device with varying core wire pitch;

FIG. 115 illustrates manufacture of a bristle device from a number ofsegments;

FIGS. 116 and 117 show another method of manufacture;

FIGS. 118 to 125 illustrate bristle devices with various drug deliveryfeatures; and

FIGS. 125 and 126 illustrate the use of a bristle device of theinvention to treat haemorrhoids

DETAILED DESCRIPTION

Referring to the drawings and initially to FIGS. 1 to 8 thereof there isillustrated a bristle device for delivery into a body lumen. The bristledevice comprises a longitudinally extending stem 1 and a plurality ofbristles extending generally radially outwardly from the stem. In theinvention there are at least two different groups or types of bristles.

In one case a prosthesis with two or more bristle fibre diameters isprovided to ensure a low profile for the device when loaded in thecatheter 5, and with sufficient anchor force to prevent migration.Smaller diameter fibre bristles 2 are intended primarily to promote andenhance thrombogenicity, while larger diameter fibre bristles 3 areintended primarily to anchor the device in the lumen to preventmigration.

Lumen occlusion occurs due to thrombogenicity of the device, which is afunction of its surface area and its ability to cause stasis. For agiven volume of fibre material, many small fibres 2 can be moreefficiently fitted into a catheter than few larger fibres 3.

Similarly, small fibres 2 are more thrombogenic per unit volume thanlarger fibres 3; as for a given volume of fibre material, there will bea greater amount of surface area for multiple small diameter fibres,than a few large diameter fibres.

FIGS. 5 and 6 illustrate a bristle device 6 with low diameter fibres 2.This enables the device to be collapsed to a low diameter, ø₁. FIGS. 7and 8 illustrate a prosthesis 7 with larger diameter fibres 3, whichwill enhance the migration prevention properties of the prosthesis. Thecollapsed diameter, ø₂, of this prosthesis is larger than ø₁.

The bristle device of FIGS. 1 and 2 has a combination of both low andhigh diameter fibres 2, 3. This enables a compromise in profile to adiameter, ø₃, where ø₁<ø₃<ø₂. This approach provides good migrationprevention properties (from large diameter fibres 3) combined with goodthrombogenicity and low profile (from the smaller diameter fibres 2).

The different bristle types can be of the same or different materials.More than one bristle material could also be used instead of, or incombination with more than one bristle diameter.

FIG. 9 illustrates another bristle device 8 according to the inventionwhich in this case has two different types of bristle interspersed andgenerally equally distributed along the length of the device. Thedifferent types of bristles may be distinguished by their dimensions ormaterial, each contributing separately in terms of anchor force andocclusion. Because of the equal distribution, the anchor force isuniformly distributed along the bristle device length as illustrated inFIG. 10.

Various alternative arrangements of different types or groups ofbristles may be provided.

For example, FIGS. 11 and 12 illustrate a bristle device 9, of length L,in which two different types of bristle are used: one for the middlesection 10 and one for the ends 11, 12. In this case, the bristles atthe ends of the device have a higher diameter. These bristles areintended to anchor the prosthesis within the lumen. The middle sectioncontains a higher density of bristles with a lower diameter, and isintended to cause more interference with blood flow along with moresurface contact with the blood and consequently, occlusion of the lumen.

FIG. 13 illustrates a bristle device 15, which has two different typesof bristle. In this case the bristles with better properties foranchoring the device in the lumen are more densely located on the lefthand side of the bristle device and taper off towards the right handside of the device where the density of the bristles of the second typeof bristles is higher. This would be advantageous in a high flowscenario requiring extremely large number of small diameter bristles tocause occlusion. By having the anchoring bristles at the end only, theother end could contain the extremely high number of lower diameterbristles required to cause occlusion, without compromising profile.Because of the distribution, the anchor force is distributed along thebristle device length as illustrated in FIG. 14.

A bristle device 16 when manufactured has an unconstrained geometry asillustrated in FIG. 15, which is the desired shape. In order to bedelivered through a catheter the bristle device must spend some time ina collapsed condition in a catheter 17 as illustrated in FIG. 16.

Storage of a device in a collapsed condition can lead to shape-settingof a bristle device, particularly if the bristles are constructed from apolymer. Specifically, once the bristle device is deployed from thecatheter it may not return fully to its original shape. Shape-settingrefers to any change in shape, which is caused due to storage a catheterfor a prolonged period. In general, the longer the period of storage thegreater the degree of shape setting is likely to be. This is shownschematically in FIGS. 17a to 17 c.

To counteract this problem, in the invention a loading system isprovided. The loading system comprises a loading tube 20. The purpose ofthe loading tube 20 is to allow the clinician to collapse a bristledevice 25 for delivery through a delivery catheter 26 immediately beforefor (temporary or permanent) implantation in a lumen. In this way thebristle device 25 will not spend a substantial amount of time in thecollapsed condition, minimising the potential for shape setting. Theloading system also comprises a loading element such as a wire 21 forloading the bristle device 25 into the loading tube 20.

The bristle device can be delivered through any suitable deliverycatheter 26. The steps for use of the loading system are as follows:

-   -   i. Bring bristle device 25 and delivery wire 21 in contact (FIG.        18)    -   ii. Screw the delivery wire 21 into the prosthesis 25 (FIG. 19)    -   iii. Using the delivery wire 21, pull the bristle device 25 into        the loading tube 20 (FIG. 20)    -   iv. Connect the loading tube 20 to a delivery catheter 26 (FIG.        21)    -   v. Push the bristle device 25 into the delivery catheter 26        using the delivery wire 21 (FIG. 22)    -   vi. Once the tip of the bristle device 25 is at the tip of the        catheter 26 (located at the distal point of the vessel intended        for implantation), holding the delivery wire 21 still, retract        the delivery catheter 26 to deploy the bristle device 25 (FIG.        23)    -   vii. Once satisfied with the position of the device 25, unscrew        the delivery wire 21 from the bristle device 25 to detach (FIG.        24)

Referring to FIGS. 25 and 26, in another embodiment, a loading tube 36of tapered geometry will allow the user to crimp down the bristle device25 to the collapsed state as it is pushed via the delivery wire into thecatheter for delivery to a vessel.

Referring now to FIG. 27 there is illustrated a bristle device 37 with adiameter larger than the lumen, deployed such that the bristles pointalong the direction of flow within the lumen. FIG. 28 shows a schematicin which a prosthesis 38 is deployed with the bristles pointing theopposite direction of the flow.

The force of the flow against the prosthesis could cause it to migrate.If the direction of flow (force) is opposite to the direction in whichthe bristles point along the lumen, the force required to move thedevice will be smaller than the case in which the direction of the flow(force) is the same as the direction along which the bristles point inthe lumen. This is due to the interaction of the tips of the bristleswith the vessel wall and the resulting friction—the tips of the bristleshelp anchor the prosthesis in the lumen if any movement of the devicebegins to occur.

As the direction of action of the flow may not always be predictable, itmay be preferable to ensure that, when deployed, the bristle device hassome bristles oriented in one direction, and other bristles oriented inthe opposite direction. A physician may wish to use different approachesto deploy the device, which may or may not lead to a desirable bristledirection with respect to the flow direction.

When a bristle device is pulled into a loading tube 20 to be pushed intoa delivery catheter 26, its bristles are aligned within the loading tubesuch that they point distally when in the catheter. This means that allbristles will point one direction when the prosthesis is deployed. Asexplained above, this means that the device will have lower force tomigration in one direction than the other.

In one embodiment of the invention a loading tube is provided which isconfigured to reorient at least some of the bristles while the bristledevice is being pushed into the delivery catheter.

Referring to FIGS. 29 to 34 in one case a loading tube 40 containsreorientation slots 41 which allow the bristles to spring out while thebristle device 25 is being pushed into the delivery catheter 26.Subsequently, as these bristles encounter the end of the slot 41 whilethe device is being pushed into the delivery catheter 26, they areforced to collapse and realign, pointing in the opposite direction tothe direction they had originally pointed.

The loading tube may be adapted to include a means to open or close thehole depending on the wishes of the physician to change or not changethe orientation of the bristles.

Ideally an embolization device should interact with the entire surfacearea of the target lumen. This has multiple benefits:

-   -   Assists denudation of the endothelium of the lumen wall, which        is known to aid in lumen embolisation.    -   Occludes the lumen along its entire length and cross sectional        area thereby preventing recanalization via a collateral or        side-branch into the target lumen.    -   Leads to a permanent occlusion thus reducing the risk of        surgical failure and the requirement for a repeat procedure.    -   Greater interaction with the vessel wall helps lock the implant        in position thereby reducing the risk of implant migration.

Removing or damaging the endothelium has a critical role to play in theclotting cascade within a lumen. When the endothelium is removed, thenormally isolated, underlying collagen is exposed to circulatingplatelets, which bind directly to collagen, which is released from theendothelium and from platelets; leading to the formation of a thrombus.If the device does not provide adequate lumen conformance and coveragethen recanalization can occur. This coverage should be maximised notonly in terms of vessel cross section but also vessel wall area also. Inspermatic vein occlusion, a liquid (e.g. sclerosant, which has greaterlumen conformance and coverage capabilities than coils) results inhigher technical success and lower recanalization rates than coils alone[8]. However, damage to the endothelium should be done without causingvessel perforation. This could lead to catastrophic events such asinternal bleeding. This is shown schematically in FIG. 35.

In another aspect of the invention a bristle device is provided whichhas a larger unconstrained diameter than the target vessel and whichincorporates bristles which are flexible enough to conform to the vesselanatomy and which will not cause vessel perforation i.e. delivery forceto the vessel wall is not sufficient to perforate.

FIG. 36 shows a prosthesis 50 for deployment in a lumen 51 with avarying lumen diameter. When deployed in a lumen with a varyingdiameter, the device can conform to the variations in the lumen diameterwithout causing lumen perforation. This is due to the flexibility of thefibres of the prosthesis which, while providing an anchor within thelumen, are not too stiff to perforate the lumen.

The potential for the fibres to perforate the vessel is dependentprimarily on the fibre material, fibre diameter and the surface area ofcontact between the fibre and the vessel wall. A fibre with a lowstiffness may have the potential to perforate the vessel if itsstiffness is high enough due to a large diameter (and potentially asharp bristle tip).

The fibres may be of a radiopaque material to enable the physician tovisualise the device using x-ray.

Material Diameter Less Than: Nitinol <0.015 Platinum <0.015 StainlessSteel <0.015 Polyester <0.015 PTFE <0.01 Nylon (Polyamide) <0.015Polypropylene <0.015 PEEK <0.015 Polyimide <0.015 Pebax <0.015Polyurethane <0.015 Silicone <0.015 FEP <0.015 Polyolefin <0.015

FIGS. 37 to 39 illustrate various embodiments in which lumens withnon-uniform diameters may be treated using a prosthesis which hasconforming geometries. FIG. 37 shows a “dog-bone” shaped prosthesis 55.FIG. 38 shows a tapered prosthesis 56 suitable for a tapered lumen. FIG.39 shows a prosthesis 57 suitable for a lumen with a step-change indiameter.

Referring to FIG. 40 in another embodiment a bristle device 58 in whichat least some of the bristles are stiffer and impose the geometry of thebristle device on the vessel wall. This occurs because the diameter ofthe bristle device is larger than that of the target vessel.

A Method to Treat Haemorrhoids

Background

Hemorrhoids, often described as “varicose veins of the anus and rectum,”are a common condition in which the veins lining the anus or lowerrectum become swollen and inflamed.

Hemorrhoids are varicosities of the hemorrhoidal plexus (rectal venousplexus). This plexus communicates with the uterovaginal plexus anddrains, via the rectal veins, into the internal pudendal vein andinternal iliac vein. Although the exact cause of hemorrhoids remainsunknown, standing too long in an upright position exerts pressure on therectal veins, which often causes them to bulge.

There are two types of hemorrhoids: external and internal, which referto their location. External hemorrhoids develop under the skin aroundthe anus; if a blood clot develops in one of them (in a condition knownas thrombosed external hemorrhoids), a painful swelling may occur.External hemorrhoids are characteristically hard and sensitive, andbleed upon rupture. Internal hemorrhoids are sac-like protrusions thatdevelop inside the rectal canal. Painless bleeding and protrusion duringbowel movements are the most common symptoms of internal hemorrhoids;however, they may cause severe pain if they become completely prolapsed,or protrude from the anal opening.

Hemorrhoidectomy, the surgical removal of hemorrhoids, is recommendedfor third- and fourth-degree internal hemorrhoids (with or withoutexternal hemorrhoids). The two major types of hemorrhoidectomyoperations are the closed (Ferguson) hemorrhoidectomy and the open(Milligan-Morgan) hemorrhoidectomy. Both techniques are performed usinga variety of surgical devices, including surgical scalpel, monopolarcauterization, bipolar energy, and ultrasonic devices.

Complications associated with Hemorrhoidectomy include [17]:

-   -   Urinary retention following hemorrhoidectomy is observed in as        many as 30 percent of patients    -   Urinary tract infection develops in approximately 5 percent of        patients after anorectal surgery    -   Delayed hemorrhage, probably due to sloughing of the primary        clot, develops in 1 to 2 percent of patients; it usually occurs        7 to 16 days postoperatively. No specific treatment is effective        for preventing this complication, which usually requires a        return to the operating room for suture ligation.    -   Fecal impaction after a hemorrhoidectomy is associated with        postoperative pain and opiate use. Most surgeons recommend        stimulant laxatives, stool softeners, and bulk fiber to prevent        this problem. Should impaction develop, manual disimpaction with        anesthesia may be required.

An alternative to hemorrhoidectomy is stapled hemorrhoidopexy, in whichan intraluminal circular stapling device resects and resets the internalhemorrhoid tissues. When the stapler is fired, it creates a circularfixation of all tissues within the purse string to the rectal wall. Ineffect, it will draw up and suspend the prolapsed internal hemorrhoidtissue.

This procedure is best utilized when offered to patients withsignificant prolapse, such as those with grade II, grade III, or IVinternal hemorrhoids. This procedure does not effectively treat mostexternal hemorrhoids, and often requires separate excision of theexternal component when performed on patients with combined disease.

Neither procedure is effective at inducing long-term relief. In arandomized trial of stapled hemorrhoidopexy versus hemorrhoidectomy, theprocedures were equally effective in preventing recurrence after oneyear [18]. Patients undergoing hemorrhoidectomy were more likely to havesymptomatic relief from the hemorrhoids (69 versus 44 percent withhemorrhoidopexy), but had significantly greater postoperative pain [18].

It has been demonstrated that embolization of the internal iliac veinsremoves reflux from hemorrhoidal plexus. Some dimishment and/ordisappearance of hemorrhoids has been associated with embolisation ofrefluxing pelvic and internal iliac veins (16). Technical success ofembolization of the internal iliac or hypogastric veins has beenreported to be 85% [9,10].

In the clinical literature, caution has been advised when embolizing theinternal iliac vein tributaries where there is clinically significantcommunication with veins of the lower limb; as this communicationbetween the obturator and the common femoral veins increases the risk ofcoil migration and displacement into a deep vein [5]. Displacement intoa deep vein can have serious consequences if the coil led to a deep veinthrombosis [5]. Accordingly, a safe and effective device is stillrequired for embolisation of the internal iliac veins for the treatmentof hemorrhiods.

In one aspect of the invention a method for the treatment ofhaemorrhoids is proposed in which a bristle device is implanted in theinternal iliac, or hemorroidal veins to cause permanent occlusion. Thisocclusion will prevent venous reflux to the hemorrhoidal plexus, whichcauses hemorroids.

FIG. 125 is a schematic showing the venous anatomy relating to thepresence of a haemorrhoid (detailed view of cross section of anus). Thebroken arrows show direction of venous reflux through internal iliacveins leading to varicosities off the haemorrhoidal plexus, causinghaemorrhoids.

FIG. 126 illustrates the insertion of bristle devices in internal iliacveins has arrested refluxing flow to the haemorrhoidal veins and causedthe haemorrhoid to disappear.

FIG. 41 shows a bristle device 60 with a length, L, and a diameter, ø.The stability of the device during and after deployment from a catheteris dependent upon the ratio of these quantities with respect to thevessel diameter. Ideally, the bristle device should have a diametergreater than or equal to the target lumen, and a length to diameterration, L/ø, of 1.0 or greater.

FIG. 42 shows a bristle device 61 with a ratio L/ø<1 deployed in alumen. The prosthesis has become unstable during, or after, deploymentand consequently now lies at an angle to the long axis of the lumen. Dueto a L/ø ratio<1 the device could migrate, recanalise or damage thelumen wall. The low length to diameter ratio also means that theprosthesis could “pop” out of the catheter making it difficult to deployaccurately to the target site.

FIG. 43 shows a bristle device 62 according to the invention withL/ø>1.0. In this case the prosthesis is correctly aligned, is stable andis unlikely to migrate or cause damage to the lumen wall.

Referring now to FIGS. 44 and 45 in this case a bristle device 63 haslonger bristles at the distal end (the end which will be deployed firstfrom the catheter). These longer bristles are intended to act as“stabilisers” upon initial partial deployment of the prosthesis. Thelonger bristles extend distally along the vessel wall providing andanchor, ensuring the prosthesis cannot “pop” forward from deliverycatheter upon completion of deployment.

The prosthesis may have stabilising bristles 65 at one or both ends of aprosthesis 64 as illustrated ion FIG. 46.

FIG. 47 shows a bristle device 71 in the collapsed configuration withina delivery catheter 72. A slot mechanism 70 is incorporated to enabledetachment once the device is fully deployed. The slot detachmentmechanism 70 may be radiopaque to enable the physician to establish theposition of the mechanism with respect to the catheter tip. FIG. 48shows the bristle partially deployed. In this configuration the slotdetachment mechanism is still engaged since the bristle device cannotmove off the axis of the delivery catheter and wire. Accordingly thephysician may still retract the bristle device at this point. FIG. 49shows the bristle device in the deployed configuration. Since thebristle device has exited the catheter it is not constrained to remainon the same axis of the delivery wire and becomes disengaged from thedelivery wire.

In another embodiment, and referring to FIGS. 50 to 52 a delivery wirewith a normally open grasping mechanism 75 illustrated. The graspingmechanism is designed to fit snugly around a ball end or lip 76 on abristle device 77. This mechanism 75 will always be open if notconstrained by the catheter wall. Once the bristle device has beenpushed out of catheter, the grasping mechanism 75 pops open detachingthe bristle device. Until this point the device can be retracted.Equally this type of mechanism could be used to retrieve the detachedbristle device by forcing the normally mechanism closed as it isretracted into the catheter.

FIG. 52 illustrates a bristle device with ball features 76 on both ends.

FIGS. 53 and 54 show a bristle device with a hook type mechanism 80 fordetachment and retrieval. The bristle device may have a hook at one, orboth ends. To ensure that lumen perforation cannot occur, the hook enddoes not project towards the lumen wall, but towards the bristle portionof the device instead.

FIGS. 55 and 56 show a bristle device with a loop type mechanism 81 fordetachment and retrieval. The bristle device can have a retrievalmechanism at one, or both ends. In this embodiment, the retrieval loopis created by forming the end of the twisted wire of the bristle burn.

FIG. 57 shows a bristle device 85 with non-uniform bristle lengths aboutthe circumference and along the device length. Variations in the bristlelength will reduce the potential for bristle device migration. FIG. 58shows the device of FIG. 57 deployed in a lumen.

-   -   Shorter bristles are less likely to buckle and can therefore        transmit a greater load to the lumen wall, increasing the radial        or “anchor” force of the device in the lumen, particularly        within non-uniform lumen diameters.    -   Imposition of undulations, roughness and non-uniformity in the        lumen wall will increase the resistance to migration of the        device due to increased friction.

FIG. 59 shows a bristle device 87 with a curved core or stem. In apreferred embodiment the core is helical, and the diameter of the helixis less than the diameter of the lumen. This configuration forces thebristles against the lumen wall, such that the radial force of thebristle device is not dependent on the outward force of the length anddiameter of the bristles alone, but also on the distance subtended bythe core to the lumen wall. This will increase the anchor force locallyand cause undulations/roughness in the lumen wall increasing theresistance to migration. FIG. 60 shows the bristle device 87 deployedwithin the lumen.

FIGS. 61 and 62 illustrate a bristle device 88 in which a core wire iscurved and the external diameter of the core is greater than that of thelumen. This configuration forces both the bristles and the core wireagainst the lumen wall. In this case the radial force of the bristledevice is a combination of both bristle and core, but is dominated byoutward force of the core.

FIGS. 63 and 64 illustrate a bristle device 89 with a curved core andnon-uniform bristle length. In this configuration, the bristle device isconfigured such that the bristle device has a curved core, and variablebristle lengths about the circumference and along the length.

FIGS. 65 and 66 illustrate another embodiment of a bristle device 90 inwhich all bristles point inward from a retaining wire. In this case thedevice is anchored entirely by the core/retaining wire.

To enable the physician to deliver the bristle device through tortuousanatomy it must be flexible. This also enables the bristle device toconform to tortuous anatomy once implanted. The flexibility of theprosthesis is defined, primarily, by properties of the core to which thebristles are attached. The flexibility of the core is a function notonly of the amount of material in the core, but also its distribution,and material (lower modulus means greater flexibility).

There are certain clinical indications where the optimal clinicaloutcome would be to simultaneously embolize a vessel and an adjoining,diverging division.

Such a clinical situation is the prophylactic embolization to preventtype II endoleak pre-endovascular aneurysm repair (EVAR). Type IIendoleaks can be identified during angiography by the presence ofcontrast travelling from a peripherally catheterized vessel into theexcluded aneurysm sac. The objective when embolizing pre-EVAR ispermanent occlusion of the internal iliac artery proximal to itsbifurcation to ensure that there is complete occlusion before proceedingto EVAR, as any leak will cause reoccurrence of the issue. Using anangled, adjacent vessel to anchor a portion of the device whiledeploying the majority of the same device in the larger vessel wouldprovide an anchor for the device, preventing future migration.

Additionally, the internal iliac vein bifurcates into anterior andposterior divisions, which supply pelvic organs as well as the glutealmuscles. It is frequently necessary to embolize one of the anterior orposterior divisions as well as the internal iliac vein. The sameapproach as described previously would be advantageous; embolizing theadjacent tributary while retracting the remainder of the device toocclude the higher order vessel.

A bristle device, which has the flexibility to be deployed acrossbifurcating vessels, may be preferable in these instances.

FIG. 67 illustrates two device prostheses of the same length withdifferent core wire diameters, ø₁ and ø₂, where ø₁>ø₂. Note: it isassumed that the core is approximately of circular cross section. Oneend of the prostheses is fixed and a load, P, is applied to the oppositeend causing deflection of the prosthesis. The deflection of the largerdiameter device, U1, is much smaller than that of the lower diameterdevice (U2).

Considering a bristle device with a stainless steel core constructedfrom twisted wire, its diameter should preferably be constructed fromtwisted wires of diameter 0.02 inches or less. Otherwise it may not bepossible to track the device to the target vessel for deployment.

In other embodiments, the flexibility of the device could be improved byhaving flexible sections 95 between device sections 96 as shown in FIG.68. Bending within the device is taken up, primarily, by the flexiblesections, which can articulate to enable it to pass through a catheterplaced in tortuous anatomy, or to be deployed in a curved vessel, oracross a bifurcation. In this case the bristle device has flexiblesections for articulation

Directional control of fluids (e.g. contrast media for angiographicvisualization, sclerosant for vessel embolization) cannot be achievedwith today's embolization technology. Currently the physician haslimited control over fluid dispersion. The current technique involvesflushing the fluid through the lumen of a catheter proximal to thetarget location.

This is of significant relevance in male and female varicoceleembolization. A varicocele is a varicose dilation of the pampiniformplexus that drains the testicle and epididymis. The pampiniform plexusdrains into the internal spermatic vein. Additional small veins draininto saphenous, external iliac, and internal iliac systems.

For specific embolization procedures e.g. varicocele, additional coilsmust be deployed in the cephalad portion of a vessel to ensure that thatthe coils occlude the main branch and all accessible collaterals [7]. Tominimize the risk of recurrence, it is often necessary to isolate themost distal (caudal) segment of the target vessel from any potentialcollateral supply. An alternative to coils is to use an occlusionballoon.

Furthermore in some patients, collateral parallel channels must beselectively catheterized and occluded, either with coils, scleroscant,glue or other embolic agents. When using sclerosants, the intention isto destroy the endothelium to expose subendothelial tissues that in turnwill lead to irreversible vascular fibrosis. For certain embolizationprocedures, e.g. varicocele, if the scleroscant migrates too distallyadverse effects can occur e.g. approximately 10% of males developtesticular phlebitis [8].

The sclerosant effect largely depends on a) the time it is in contactwith the endothelium and b) the volume and rate of injection [8].Controlling these variables significantly influence the outcome and alsothe propensity to damage adjacent non-target vessels.

This proximal migration of the fluid is often referred to as reflux. Insome cases, this fluid may contain a drug, sclerosant, fibrin, thrombin,glue, alcohol, beads, or drug coated beads. The physician may requireaccurate delivery of these agents to prevent non-target therapy.

In the invention a bristle device may be used to prevent proximalmigration of a fluid during delivery using a catheter.

When implanted, a bristle device causes a resistance to flow through thedevice. Similarly, the construction of the device itself means that flowis initiated within the device itself, the flow will have a lowerresistance laterally than axially, and will be inclined to fill up anyavailable space outside of the device rather than travel axially throughthe device itself. Consider the following steps in order to inject afluid into a vessel, wherein the direction of the flow is controlledusing a bristle device.

-   1. A bristle device is deployed distal to the location in which it    is intended to deliver the fluid-   2. The bristle device is crossed using a catheter such the tip of    the catheter resides on the distal side of the bristle device.-   3. The fluid is injected through the catheter tip. It is prevented    from migrating through the bristle device and will fill any vessels    distal to the device.

FIG. 69 illustrates a bristle device 97 in use to prevent proximalmigration of a fluid during delivery using a catheter.

In another embodiment, without the presence of individual bristlesegments, the path of least resistance for flow is still laterally. Thisis because the density of bristles laterally is lower than thatproximally and distally. Accordingly, the flow will naturally belaterally from the catheter tip. This enables treatment of a collateralvessel and is shown schematically in FIG. 71. FIG. 71 illustrates theuse of a bristle device 98 to ensure lateral dispersion of a fluid.Note: Section A-A shows a much higher density of fibres meaning flowwill have a higher resistance in this direction (axially) compared tolaterally (Section B-B).

The presence of these gaps between the brush segments is also a means toreduce the profile of the bristle device when constrained for placementin a catheter. This is because effect of bristles lying on top of oneanother, increasing profile is limited.

Referring to FIG. 72 in another embodiment, to further improve theability of a bristle device 99 to prevent longitudinally flow (ensurelateral dispersion of a fluid), bristles with a rectangular crosssection 100 are illustrated. The bristles are aligned such that the longaxis of the bristle is perpendicular to the centreline of the mainvessel. These bristles mean that the path of least resistance islaterally rather than distally or proximally. This can be observed byviewing Section A-A and B-B in FIG. 72. Clearly, it will be easier for afluid to pass through B-B than A-A due to the geometry of the bristles.

A blood vessel wall is composed of three layers. The innermost layer iscalled the endothelium and is merely a layer of endothelial cells. Themiddle and outer layers are known as the medial and adventitial layersrespectively.

It has been shown that denudation, or damage to the endothelial liningof a blood vessel can induce vasospasm, and inflammatory reactionsleading to vessel occlusion. Removing or damaging the endothelium has acritical role to play in the clotting cascade within a vessel. When theendothelium is removed, the normally isolated, underlying collagen isexposed to circulating platelets, which bind directly to collagen, whichis released from the endothelium and from platelets; leading to theformation of a thrombus.

Preferably, in order to induce the greatest damage to the endothelium, abristle device should have a large number of fibres in contact with thelumen wall per unit surface area. Embolization coils do not causesignificant denudation to the vessel wall as the degree of wall contactis minimal. This can be seen in FIG. 73.

In order for a bristle device 101 to cause significant denudation of avessel wall it should have a greater diameter than the vessel in whichit is implanted. This ensures a larger contact area between fibres andthe vessel wall as shown in FIGS. 74 and 75.

Similarly, a greater number of fibres in contact with the vessel wallwill have a greater impact in causing denudation and inducingembolisation. This is shown schematically in FIG. 76. This can beexpressed in terms of the bristle length or area in contact with thevessel wall, per unit surface area of the vessel wall.

In some embodiments of the invention we provide

-   -   a bristle device for embolisation with a device diameter to        vessel diameter ratio of 1.1 or greater and/or    -   a bristle device a minimum length of bristle of 1 mm in contact        with a vessel surface area of 2 mm² and/or    -   a minimum of 0.1% of the vessel surface area in contact with the        bristle device fibres.

In another embodiment, the bristle device could be used for denudationof the vessel wall by advancing, retracting and rotating the bristledevice at the site of treatment. Once denudation is complete, theprosthesis can be left behind to promote permanent occlusion. FIG. 77 isa schematic showing denudation of the endothelium using translation androtation of a bristle device 105. This “polishing” action will helpstrip the endothelial cells from the vessel and enhance the potentialfor vaso-occlusion. Once complete the prosthesis can be detached fromthe delivery wire and left in place.

The bristle devices of the invention are also suitable for the treatmentof septal defects and patent foramen ovale.

Emboli leading to stroke or to transient ischemic attack can originatein either the systemic venous circulation (paradoxical emboli) or in thesystemic arterial circulation. Some patients with cryptogenic strokehave a patent foramen ovale (PFO), an atrial septal defect (ASD), or anatrial septal aneurysm (ASA) that can be identified by echocardiography.These structures have been implicated in the pathogenesis of embolicevents, leading to stroke.

Paradoxical emboli: a paradoxical embolus originates in the systemicvenous circulation and enters the systemic arterial circulation througha PFO, atrial septal defect, ventricular septal defect, or extracardiaccommunication such as a pulmonary arteriovenous malformation [10]. Theembolus can originate in veins of the lower extremities, in pelvicveins, in an atrial septal aneurysm, or from a clot around the edges ofa PFO [10]. Patients with paradoxical emboli can present withcryptogenic stroke.

PFO and ASD: The foramen ovale and its flap-like valve between the rightand left atrium are important components of the fetal circulation. Inthe developing fetus, oxygenated blood from the umbilical vein entersthe right atrium via the inferior vena cava and is shunted into the leftatrium, circumventing the non-inflated lungs. After birth, a relativeincrease in left atrial pressure closes the flap, and adhesionsfrequently result in a structurally intact atrial septum. However, inapproximately 25 percent of adults, the foramen ovale remains patent andacts as a potential right-to-left shunt [10].

The closure devices commonly used for percutaneous PFO repair includeoccluders made of two wire mesh discs filled with polyester fabric. Thedevice is folded into a special delivery catheter, advanced into theheart and through the defect. When the catheter is in the properposition, the device slowly is pushed out of the catheter until thediscs of the device sit on each side of the defect, like a sandwich. Thetwo discs are linked together by a short connecting waist. Over time,heart tissue grows over the implant, and it becomes part of the heart.

Complications associated with trans-catheter closure of a PFO/ASDinclude device embolization or malposition, arrhythmias (usually atrialbut include sudden death), and device erosion/perforation [11].

Referring to FIG. 78 a bristle device 110 suitable for occlusion septaldefects of a patent foramen ovale is shown. The bristle device comprisesat least two distinct device sections, which are connected via a core.Referring to FIG. 79, the device 110 is shown in a tilted configurationhighlighting the flexibility of the device. This flexibility will enablethe device to conform to the anatomy of the patient, and will ensuregood trackability of the device during delivery. The bristle device 110can be used for septal defect and PFO occlusion. FIGS. 78 and 79 show aseptal defect or PFO device 110 which can articulate/bend depending onthe target anatomy.

FIGS. 80 and 81 illustrate a septal occlusion device 115, which canstretch depending on the target anatomy (thickness of the septal wall).

Referring to FIGS. 82 to 85 the implantation of the device 110 or 115 isillustrated. In FIG. 82 a catheter is shown advanced through the rightatrium via the inferior vena cava. In FIG. 83 a segment of the device isshown partially deployed. This first segment will provide an anchor onthe left atrium side of the patent foramen ovale. FIG. 84 illustratesone segment of the bristle device fully deployed within the left atrium.FIG. 85 illustrates the bristle device fully deployed.

Current technology foreshortens significantly upon deployment into avessel, between 30-50%, this intended approach attempts to ensure thatthe pre-shaped coil snaps into its set shape when deployed into a vesseland adheres to the vessel wall [13].

With the exception of glue, which is occasionally used, there is notechnology on the market today that does not use this approach.

Therefore it is difficult to embolize the entire length of a largevessel (>10 cm) with technology available today as complete vesselocclusion cannot be achieved and is cost prohibitive.

Additionally there is no product on the market today that canaccommodate variable lengths peri-procedurally. This would beadvantageous for three reasons:

-   -   Significantly reduce inventory requirements and range of        products to be manufactured    -   Allows the physician to precisely occlude the portion of the        vessel that requires occlusion    -   Allows a physician to occlude a bifurcation, feeder vessel or        tributary that may contribute towards recanalization

FIGS. 86 and 87 illustrate a bristle device 120 with length modifyingcomponents 121 that can be extended or retracted intraluminally toadjust the device to the requirements of the target vessel

FIG. 88 illustrates deployment of a first bristle bundle into the lumenof the target vessel. Also illustrated is a technique of retractingdelivery catheter to extend adjustable section between bristle bundles.

FIG. 89 illustrates an alternative embodiment depicting a loosely woundcore 125 that accommodates compression of bristle bundles intraluminally

FIG. 90 illustrates technique of pushing a delivery catheter 126 forwardto decrease adjustable sections between bristle bundles.

In order to induce stasis and cause thrombus formation, ideally nothrough flow path should exist in the prosthesis that permits blood toflow uninhibited from one end to the other. In reality, some flow pathmay exist which forces the blood to travel a tortuous path past theprosthesis bristles. If a low resistance flow path is present, occlusionmay not occur.

For a bristle device, manufactured using a twisted wire approach, thebristles effectively define a helical surface. The negative of thishelical surface defines a flow path.

By its nature, a bristle device may have a through flow path as shown inFIG. 91(a). This will cause turbulent flow and force the blood tointeract with a greater surface area of the device, inducing thrombusformation and occlusion. A more tortuous path is shown in FIG. 91(b).

FIG. 91 illustrates a bristle device 130 with a through flow path. Pathis shown adjacent to the bristle device using the arrow. This path couldbe described as the inverse of volume of the device. This tortuosity ofthis flow path is defined by the pitch and radius of the helix, whichdefines the flow path as shown in FIG. 92.

A longer pitch, p, with a small radius, r, will mean a relatively easyand straight flow path. A short pitch with a large radius will imply alonger tortuous flow path. If a flow path does exist, this should be astortuous and as long as possible to cause occlusion.

Preferably, for inducing occlusion of a blood vessel, the ratio of thepitch to the radius, p/r, of the flow path should be 50 or less. Morepreferably, the ratio of the pitch to the radius, p/r, of the flow pathshould be 10 or less. More preferably, the ratio of the pitch to theradius, p/r, of the flow path should be 1 or less. More preferably, theratio of the pitch to the radius, p/r, of the flow path should be 0.5 orless.

If a twisted wire manufacturing approach is used, the ratio of the pitchto the radius of the helix should be such that the adjacent bristlesections of a bristle device 140 overlap as shown in FIG. 93.

FIG. 93 illustrates overlapping bristle sections to inhibit flow paththrough device.

Another means of ensuring overlapping bristles is to form the deviceusing pre-shaped bristles e.g. saw tooth or spiral, which would increaseinteraction between bristles.

In FIG. 94 a bristle device is shown in which, upon coming in contactwith a fluid or blood, the fibres 150 swell up increasing in volume inorder to further occlude the lumen in which they reside. This processcould be initiated before deployment in the body, or while the bristledevice is in its collapsed condition in a catheter/loading tube, asshown in FIG. 94. Similarly, the fibres could be intended to absorb adrug when increasing in volume. This drug would then be delivered to thevessel wall once the bristle device is deployed. FIG. 94 illustratesfibres that increase in volume when in contact with a fluid and or theblood.

In another embodiment, the bristles could have micro fibres 160 in orderto increase thrombogenicity and reduce flow path. This is shownschematically in FIG. 95.

Due to adjacent vessel blood flow, an embolus could break away from theclot within the bristle device. The maximum potential size of an emboluswhich could break away from the bristle device is dictated by thedensity of the bristles in the device, i.e. the cavities within whichthrombus can form in the device. This is defined by the distance betweenadjacent bristles. Similarly, the ability of the bristle device to causevessel occlusion can be improved by reducing the distance betweenadjacent bristles.

Pulmonary Embolism

A common vessel for embolisation is the gonadal vein (for the treatmentof varicocele, pelvic vein competence). An embolus could detach from abristle device, which has been deployed in the proximal portion of agonadal vein close to the renal vein. This embolus can then travel viathe left common iliac vein through the inferior vena cava into the rightatrium of the heart. This could potentially travel into the pulmonaryarteries causing a pulmonary embolism. In about 5% of people in whomautopsy is done to elucidate the cause of death, pulmonary embolism isunexpectedly found to be the cause. Gardner suggests that the clot sizeshould be limited to 4.5 mm or less using clips in order to prevent alethal pulmonary embolism [19].

Peripheral Arterial

Ideally any embolus which could break away from the embolisation deviceis small enough so that it can be thrombolyzed by the body's owndefences and remain clinically asymptomatic. A large embolus could causetissue ischemia and infarction. In 1989, Kazmier proposed aclassification for disseminated peripheral atheroembolization into threemajor clinical presentations: peripheral syndrome, renal syndrome, andvisceral syndrome [20]. By definition, microemboli representatheromatous material with a size less than 1 mm. Accordingly themaximum size embolus which can be permitted to break away from theocclusion device should be less than or equal to 1 mm. To ensure this,the maximum dimension between adjacent bristles which define the cavityfrom which an embolus could break away should be 1 mm or less. Anembolus from a bristle device deployed in the internal iliac arterycould enter the common iliac and travel distally to the smaller lumenssuch as the popliteal and tibial or pedal arteries (shown in FIG. 64). Ablockage of these lumens can cause ischemia of the foot, a phenomenonknown as trash foot. FIG. 96 shows an embolus detaching from a bristledevice which has been deployed in the left internal iliac artery.

Cerebral

The effect of an embolus may not be confined to the peripheralcirculation. In the case of the cerebral lumens, an embolus of 1 mm orless may not be tolerated, as emboli of this size can cause a stroke.For aneurysm treatment, the maximum acceptable diameter should be lowerthan 1 mm. For the case of embolic filters, used to capture emboli whichoccur during carotid stenting, the pore sizes are approximately 0.8 mmin diameter [21]. Accordingly the gap between the bristles in thedeployed configuration should be 0.8 mm or less. FIG. 97—shows a bristledevice deployed to treat a cerebral aneurysm. An embolus has broken awayfrom the bristle device which could cause stroke.

In the invention, and referring to FIGS. 98 to 100 to prevent pulmonaryembolism a bristle device 170, 171, 172 has gaps between adjacentbristles to limit clot fragments to 4.5 mm or less. To prevent potentialfor peripheral microembolism the bristle device should have gaps betweenadjacent bristles of 1 mm or less. For the prevention of cerebralinfarction events, the bristle device should have gaps between adjacentbristles of 0.8 mm or less.

FIGS. 98 to 100 illustrate gaps between bristles dictate the potentialemboli which could detach form the bristle device. A=4.5 mm, B=1.0 mm,C=0.8 mm.

Ideally medical devices that come in contact with a vascular wall or aredeployed endovascularly require features that ensure they do notperforate or puncture the vessel wall. Perforations can lead to hematomaand other serious adverse events. It is critical for devices to reducethe risk of internal wall damage. This also provides the clinician withconfidence to advance the device against resistance, knowing that thedevice will not induce trauma. FIGS. 101 to 104 show various bristletips to prevent vessel perforation upon or after deployment. (i) softspring 180 (FIG. 101), (ii) soft flexible tips (e.g. made from apolymer) 181 (FIG. 102), (iii) bristles at end of bristle device tied tomake an atraumatic end 182 (FIG. 103), (iv) bristles 183 naturallyprotrude from the end of the device (FIG. 104).

FIGS. 101 to 104 illustrate various embodiments of atraumatic distal andproximal ends designed to prevent vessel wall perforation

During percutaneous endovascular treatment an embolization coil istypically delivered to a desired location in the vasculature of apatient through the use of a catheterization procedure. In thisprocedure, a catheter is inserted into the vasculature of a patient andpositioned to be proximal or distal to the targeted anatomical location.Generally, an embolization coil is loaded into the lumen of the catheterand advanced through the catheter using a pusher rod until it reachesand exits through the distal end of the catheter.

Unless “detachable” coils are used this device cannot be repositioned orretrieved once deployed. This technique suffers from difficultyassociated with the precise and controlled placement of the embolizationcoil. Accordingly, there exists a need to develop and provide a systemor mechanism for the placement of an embolization coil into thevasculature of a patient that can be done in a precise and controlledmanner, while maintaining cost effectiveness, simplicity, reliability,and manufacturability.

FIG. 105 (a) shows an assembly wherein the bristle device 200 isattached to a delivery wire 201 via a screw mechanism 202. In thisassembly detachment is accomplished by unscrewing the delivery wire fromthe bristle device as shown in FIG. 105 (b).

The interaction of the device, which is constrained radially at least tosome extent within the lumen, causes an interference fit. Thisinterference fit occurs due to the propensity of the lumen to try alter(reduce) the diameter of the bristle device, and the propensity of thebristle device to try to alter (increase) the lumen diameter.

The classic relation describing the holding torque of an interferencefit assembly using that the assumption that the surfaces have noirregularities and that the contact pressure at the interface isuniformly is distributed, is as follows (Mascle et al., 2011):T_(holding)αμ_(s)d_(sh)pA

This implies that the holding torque, T_(holding), or torque required tocause a rotation of the bristle device within the lumen is proportionalto the coefficient of static friction between the bristle device and thelumen wall, μ_(s), the diameter of the lumen, the interference pressure,p, and the area of contact, A.

This implies that interference pressure is a function of the outwardradial force of the device against the pressure. The coefficient ofstatic friction between the bristle device and the lumen wall is afunction of the lumen and bristle device materials, their roughness andthe topography of the geometry which results when the bristle device isdeployed within the lumen.

In order to allow detachment of the bristle device from the deliverywire once it has been deployed in the lumen, the torque to unscrew thedelivery wire from the bristle device must not exceed the holding torqueof the bristle device in the lumen, i.e. T_(holding)>T_(unscrew). If theholding torque does not exceed the torque required to unscrew thedelivery wire from the bristle device, the bristle device will simplyrotate within the lumen and detachment may not occur.

FIG. 106 shows a bristle device 210 deployed in a lumen. Section Arepresents a cross section within the bristle device. Section Brepresents a cross section at the level of the delivery wire proximal tothe detachment mechanisms.

In FIG. 106 (b), the behaviour of the bristle device 210 is shown whenno twist is applied to a delivery wire 211 (top). The middle schematicshows the behaviour when some twist is applied to the delivery wire 211causing the bristle device 210 to rotate within the lumen (undesirable).This occurs because the holding torque of the bristle device does notexceed the torque required to unscrew the bristle device from thedelivery wire. In the bottom schematic upon rotation of the deliverywire, no rotation of the device occurs since the holding torque of thebristle device exceeds the torque required.

When coils migrate to unintended locations, they are required to beremoved to prevent non-target embolization, tissue ischemia and/orerosion. In general removal of coils is attempted via a percutaneousendovascular approach, by placing a guiding catheter close to themigrated coils and extracted by using a forceps or gooseneck snare tograsp the coil. Technically, removal of coils is very challenging andcan take dozens of attempts with various devices to remove [22].

Complications of coil retrieval are significant and can involve [8]:

-   -   Disturbing the rest of the coil nest and exacerbating the        problem.    -   Damaging other vessels: dissection, occlusion, spasm, rupture of        the vessel caused by manipulation of the retrieval device.    -   Cardiac arrhythmias if the coil has migrated to the heart.    -   Embedding or further distal embolization of the coil or device

In the invention we provide a bristle device in which the diameter(size) of the core is greater than that of the core of the bristledevice. This enables the bristle device to be retrieved easily using agooseneck or snare type device.

FIG. 107 shows how a retrieval device 220 can easily grasp a bristledevice 221 at the screw detachment mechanism. In the top schematic theretrieval device has been deployed from its delivery catheter. In themiddle schematic the bristle device detachment mechanism has beengrasped in the wire “snare” of the retrieval device and is beingretracted into the catheter. The bottom schematic shows the finalretraction of the bristle device, now almost entirely in a collapsedcondition, into the catheter.

FIG. 108 shows a bristle device 230 with a screw detachment mechanism231 at both ends. This can be retrieved from a distal or proximalapproach.

Migrated coils are generally retrieved using a forceps or a goosenecksnares. These are expensive devices and can significantly add to theprocedural cost. It would be advantageous if a coil could be grasped andremoved without the necessity to use additional retrieval devices. Inthe embodiment shown in FIG. 109, the screw detachment mechanism isshaped to guide the delivery wire into the thread to be screwed to thewire and retrieved.

In some cases, it is unnecessary or undesirable to permanently occlude ablood vessel. In these circumstances, using an agent which causestemporary vascular occlusion may be preferable.

Circumstances in which temporary agents may be indicated [8]:

-   -   Pre-operative embolization: e.g., embolization of a renal tumor        immediately before resection. In these circumstances, there is        no advantage in permanent obliteration of the tumor circulation        and any non-target embolization is less likely to be harmful.    -   Trauma: it is usually only necessary to arrest bleeding until a        stable clot forms and the vessel can heal.    -   Upper gastrointestinal tract hemorrhage.

Temporary embolization agents are most beneficial when a vessel cansafely be sacrificed but permanent occlusion is not necessary (e.g.,internal bleeding associated with trauma). Having a biodegradableembolization device that provide temporary embolization, relieves theclinical issue, and then safely degrades over a specific time periodproviding the opportunity for systemic blood flow to be restored wouldbe a significant clinical advancement.

In other circumstances, it may be preferable that once embolisation hasoccurred, that the device, or a portion of the device, biodegradesmeaning that the implant:

1. Has no structural role integrity, and therefore does not interferewith surrounding tissues

2. Is no longer present in the body

In the invention, either the core, or the bristles, or both the bristlesand the core could be biodegradable or absorbable.

The biodegradable/absorbable elements of the device may be composed ofsynthetic polymers (Poly-lactic acid (PLA) and its isomers andcopolymers, Poly-glycolic acid [PGA], Poly-caprolactone [PCL], Polydioxanone, Poly-lactide-co-glycolide) or Magnesium alloys. This is shownin FIGS. 110 to 112.

FIG. 110 (i) a bristle device 250 on implantation, (ii) thrombus formedin the bristle device, (iii) core begins to degrade, (iv) core fullydegraded leaving only thrombus interspersed with bristles supporting thethrombus

FIG. 111 (i) a bristle device 260 on implantation, (ii) thrombus formedin the bristle device, (iii) bristles begins to degrade, (iv) bristlesfully degraded leaving only thrombus a supporting core

FIG. 112 (i) a bristle device 270 on implantation, (ii) thrombus formedin the bristle device, (iii) core and bristles begin to degrade, (iv)bristle device fully degraded leaving only thrombus within the vessel

A number of methods of manufacture may be used to make the prosthesis.FIG. 113 shows a twisted wire device 280 manufactured using a twistedwire method. The fibres are placed between two parallel wires. Thesewires are fixed at one end and twisted at the other. Upon twisting thewires are formed into a helix causing the bristles to translate frombeing parallel to being rotationally offset from one another forming adevice like construct.

In another embodiment variations in the bristle density can be achievedby varying the pitch of the twisted wire which the holds the bristles inplace. This is shown schematically in FIG. 114. FIG. 114 illustrates atwisted wire device with varying core wire pitch in order to vary thedensity of the bristles.

FIG. 115 shows a series of individual segments which in this case areextrusions 290, each of which has an array of long elements projectingfrom the centre. Upon connection of these constructs, a prosthesis 295suitable for lumen occlusion can be constructed. FIG. 115 illustratesmanufacture from a series of device segments, or extrusions.

FIGS. 116 and 117 illustrates a method of manufacture in which theentire device is one piece is by cutting the fibres from a core 300.This could also be constructed by laser cutting the tube and passing andexpanding element through the lumen to splay out the fibres.

A bristle device may also be used as a platform for therapeuticdelivery. This could be an agent to augment thrombogenicity (sclerosant,fibrin, thrombin, glue, alcohol), or to delivery an oncologic drug totreat a tumour, or a device to aid in radiofrequency ablation. This isshown schematically in FIG. 118. The elution time of such an agent couldbe seconds, hours, days, or years. The coating could be fluid or solid.

FIGS. 118-119 illustrate delivery of the drug to the vessel wall once abristle device 320 is in place.

In one embodiment, the device is coated with a drug, or sclerosant, justbefore being pushed into the catheter (FIG. 120). This drug orsclerosant is then delivered to the vessel wall once it is deployed atthe target site. This is shown schematically in FIG. 120. FIG. 120illustrates flushing of bristle device with a therapeutic prior to beingpushed to target vessel. The detailed view shows a coating of the drugon the device fibres following flushing.

The bristles of the bristle device could be further enhanced usingstriations or holes which can contain a therapeutic. This could increasethe volume of therapeutic on the bristle, and to further control itselution over time by restricting the area from which the therapeutic candissolve, elute.

FIGS. 121 to 123 illustrates bristles that are enhanced using pores,striations or holes to hold drug for elution over time.

The invention also provides a “perfusion bristle device”. This bristledevice 350 contains a channel 351 through the centre for flow. As theflow passes the bristles the therapeutic is transferred to the flow,allowing a distal therapy to be delivered. FIG. 124 illustrates the useof a perfusion bristle device for delivery of a drug.

REFERENCES

-   1. The Technology of Expansion. Terumo Interventional Systems.    Downloaded on Feb. 21, 2013 from    http://www.terumois.com/products/embolics/AZUR.aspx-   2. Ekeh et al., Complications arising from splenic artery    embolization: a review of an 11-year experience. The American    Journal of Surgery, 205, 250-254, 2013-   3. Ryer et al. 2013, Comparison of outcomes with coils versus    vascular plug embolization of the internal iliac artery for    endovascular aortoiliac aneurysm repair. Journal of Vascular    Surgery, Volume 56, Issue 5, November 2012, Pages 1239-1245.-   4. Rastogi et al., Unintended coil migration into the right    ventricle during the right ovarian vein coil embolization. Vascular    and Endovascular Surgery, 2011 October; 45(7).-   5. Marsh et al., Coil Protruding into the Common Femoral Vein    Following Pelvic Venous Embolization. Cardiovascular Interventional    Radiology (2008) 31:435-438-   6. Beddy et al., Testicular varicoceles. Clinical Radiology (2005)    60, 1248-1255-   7. Beecroft et al., Percutaneous varicocele embolization. Canadian    Urological Association Journal. September 2007, Volume 1, Issue 3-   8. Kessel et al., Transcatheter Embolization and Therapy. Springer    ISBN 978-1-84800-896-0. Published 2010-   9. Balian et al. Pelviperineal venous insufficiency and varicose    veins of the lower limbs. Phlebolymphology. 2008; 15(1):17-26.-   10. Messé et al., Atrial septal abnormalities (PFO, ASD, and ASA)    and risk of cerebral emboli in adults. Downloaded on Feb. 22, 2013    from www.uptodate.com-   11. St. John Sutton et al., Devices for percutaneous closure of a    secundum atrial septal defect. Downloaded on Feb. 22, 2013 from    www.uptodate.com-   12. Letourneau-Guillon et al., Embolization of Pulmonary    Arteriovenous Malformations with Amplatzer Vascular Plugs: Safety    and Midterm Effectiveness. Journal of Vascular and Interventional    Radiology, Volume 21, Issue 5, Pages 649-656, May 2010.-   13. Wang et al., The Amplatzer Vascular Plug: A Review of the Device    and its Clinical Applications, CardioVascular and Interventional    Radiology, August 2012, Volume 35, Issue 4, pp 725-740.-   14. Yoo et al., Preoperative portal vein embolisation using an    amplatzer vascular plug. European Radiology (2009) 19: 1054-1061.-   15. Pelage et al. What is Azur Hydrocoil and How Does it Work?    Presented at Society of Interventional Radiology, 2011.-   16. Van Der Vleuten et al., Embolization to treat pelvic congestion    syndrome and vulval varicose veins. International Journal of    Gynecology and Obstetrics 118 (2012) 227-230-   17. Bleday et al., Treatment of haemorrhoids, Sep. 24, 2012.    Downloaded on Feb. 22, 2013 from www.uptodate.com-   18. Nyström et al., Randomized clinical trial of symptom control    after stapled anopexy or diathermy excision for haemorrhoid    prolapse. Br J Surg. 2010; 97(2):167.-   19. A M Gardner, Inferior vena caval interruption in the prevention    of fatal pulmonary embolism, American Heart Journal (impact factor:    4.65). July 1978; 95(6):679-82.-   20. Kazmier F J.; Shaggy aorta syndrome and disseminated    atheromatous embolization. In: Bergan J J, Yao J S T, editors Aortic    surgery Philadelphia: WB Saunders; 1989. p. 189-94.-   21. Chung E M, Hague J P, Evans D H., Revealing the mechanisms    underlying embolic stroke using computational modelling, Phys Med    Biol. 2007 Dec. 7; 52(23):7153-66. Epub 2007 Nov. 19.-   22. Pyung et al., Successful percutaneous endovascular retrieval of    a coil in the left ventricle which migrated during embolization for    pulmonary arteriovenous malformation. International Journal of    Cardiology 163 (2013) e33-e35

Modification and additions can be made to the embodiments of theinvention described herein without departing from the scope of theinvention. For example, while the embodiments described herein refer toparticular features, the invention includes embodiments having differentcombinations of features. The invention also includes embodiments thatdo not include all of the specific features described.

Any aspect set forth in any embodiment may be used with any otherembodiment set forth herein. Every device and apparatus set forth hereinmay be used in any suitable medical procedure, may be advanced throughany suitable body lumen and body cavity, and may be used for treatmentor observation of any suitable body portion.

The many features and advantages of the present disclosure are apparentfrom the detailed specification, and thus, it is intended by theappended claims to cover all such features and advantages of the presentdisclosure that fall within the true spirit and scope of the presentdisclosure. Further, since numerous modifications and variations willreadily occur to those skilled in the art, it is not desired to limitthe present disclosure to the exact construction and operationillustrated and described, and accordingly, all suitable modificationsand equivalents may be resorted to, falling within the scope of thepresent disclosure.

The invention is not limited to the embodiment hereinbefore described,with reference to the accompanying drawings, which may be varied inconstruction and detail.

The invention claimed is:
 1. A bristle embolization device for deliveryinto a body lumen comprising a longitudinally extending stem and aplurality of bristles extending generally radially outwardly from thestem wherein there are at least two different groups or types ofbristles, wherein one group of bristles are aligned to point in a firstlongitudinal direction of the stem and another group of bristles arealigned to point in a second longitudinal direction of the stem which isopposite the first longitudinal direction, wherein at least one group ofbristles is adapted for occlusion of a lumen to create an embolization,wherein at least one group of bristles are adapted for anchoring thebristle device in a body lumen, wherein the bristle embolization devicehas a surface area, and wherein lumen occlusion occurs due tothrombogenicity of the bristle embolization device which is a functionof the surface area; wherein the bristle embolization device has alength, L, and a diameter, Θ, the bristle embolization device having alength to diameter ratio of L/Θ of greater than or equal to 1.0; andwherein the at least one group of bristles adapted for occlusion of alumen are configured so that they are in circumferential contact withthe lumen to occlude a cross sectional area of the lumen and to causedenudation of an endothelium layer of the lumen.
 2. The bristleembolization device of claim 1 wherein bristles of one group have athickness which is different than the thickness of bristles of anothergroup.
 3. The bristle embolization device of claim 1 wherein one groupof bristles is of a different material than the material of anothergroup of bristles.
 4. The bristle embolization device of claim 1 whereinone group of bristles is more flexible than another group of bristles.5. The bristle embolization device of claim 1 wherein one group ofbristles are interspersed with another group of bristles.
 6. The bristleembolization device of claim 1 wherein the at least one group ofbristles are adapted for anchoring the bristle device in a body lumen isprovided at the proximal and/or distal end of the device.
 7. The bristleembolization device of claim 1 wherein the occlusion group of bristlesare located intermediate the proximal and distal ends of the bristledevice.
 8. The bristle embolization device of claim 1 wherein some ofthe occluding group of bristles are interspersed with the anchoringgroup of bristles so that the number of occluding bristles increasesform the distal end towards the proximal end of the device.
 9. Thebristle embolization device of claim 1 wherein one group of bristlesextend radially outwardly to one diameter and another group of bristlesextend radially outwardly to another diameter which is different thanthe diameter of the first group of bristles.
 10. The bristleembolization device of claim 1 wherein one group of bristles are aligneddifferently than another group of bristles.
 11. The bristle embolizationdevice of claim 1 wherein at least some of the bristles are adapted fordelivery of a therapeutic agent.
 12. The bristle embolization device ofclaim 11 wherein the bristles adapted for delivery of a therapeuticagent are at least partially coated with a therapeutic agent.
 13. Thebristle embolization device of claim 11 wherein the bristles comprisestriations and/or holes for containing a therapeutic agent.
 14. Abristle embolization device loading system comprising: a bristle devicefor delivery into a body lumen; a loading tube; and a loading elementfor loading the bristle device into the loading tube; wherein thebristle device comprises a longitudinally extending stem and a pluralityof bristles extending generally radially outwardly from the stem,wherein there are at least two different groups or types of bristles,and wherein one group of bristles are aligned to point in a firstlongitudinal direction of the stem and another group of bristles arealigned to point in a second longitudinal direction of the stem which isopposite the first longitudinal direction, wherein at least one group ofbristles is adapted for occlusion of a lumen to create an embolization,wherein at least one group of bristles are adapted for anchoring thebristle device in a body lumen, wherein the bristle embolization devicehas a surface area, and wherein lumen occlusion occurs due tothrombogenicity of the bristle embolization device which is a functionof the surface area; wherein the bristle embolization device has alength, L, and a diameter, Θ, the bristle embolization device having alength to diameter ratio of L/Θ of greater than or equal to 1.0; andwherein the at least one group of bristles adapted for occlusion of alumen are configured so that they are in circumferential contact withthe lumen to occlude a cross sectional area of the lumen and to causedenudation of an endothelium layer of the lumen.
 15. The bristleembolization device loading system of claim 14 wherein the loadingelement is detachably mountable to the bristle device.
 16. The bristleembolization device loading system of claim 14 wherein the loadingelement comprises a loading wire.
 17. The bristle embolization device ofclaim 1 wherein the stem comprises a flexible section.
 18. The bristleembolization device loading system of claim 14 wherein the stem of thebristle device comprises a flexible section.
 19. The bristleembolization device of claim 1, wherein the at least one group ofbristles adapted for anchoring the bristle device in a body lumen areconfigured so that while anchoring the device in a body lumen they donot perforate a lumen wall.
 20. The bristle embolization device loadingsystem of claim 14, wherein the at least one group of bristles adaptedfor anchoring the bristle device in a body lumen are configured so thatwhile anchoring the device in a body lumen they do not perforate a lumenwall.